The Role of Perinatal Cardiology in Saving the Life and Its Quality of Fetuses, Newborns and Children (on the Basis of Own Experience and Review of The Literature)

Abstract The role of prenatal cardiology and the organization of perinatal cardiological centers in early diagnostics and early therapeutic procedures in fetuses and newborns with cardiac malformations and circulatory disturbances was discussed on the basis of the literature and own experience. The possibilities of an early perinatal diagnosis and early therapeutic approaches to cardiac defects were presented. It was stressed that there is a necessity to broaden the educational aims in these areas and in the near future to prepare multidisciplinary teams working together in specialist centers.

INTRODUCTION e recent huge medical progress enables us not only to save life but also to ensure its high quality. e major role in making this possible is played by the early diagnosis of a disease and an early therapeutic approach. To obtain this goal in fetuses and neonates, prenatal care and perinatal centers are necessary. e majority of human malformations arise between the 4th and 6th week of pregnancy [1]. At the 8th week of pregnancy, embryogenesis is nished. Currently, the rst prenatal examination of fetuses is possible around the 12th week of pregnancy ( Figure 1) (Earlier scans at 4-6-8 weeks are performed only to con rm the presence of pregnancy, its location and whether it is single or multiple). Some 10-15 years ago a rule was introduced by Professor M. Hansmann, founder of the German Prenatal Ultrasonography School, that the rst sonographic examination should be performed at the 10th week of pregnancy, which was widely used [2]. In contrast, Professor K. Nicolaides, founder of the Fetal Medicine Foundation, suggested that delaying the rst sonographic examination until the 12th week of gestation may provide more data on the development and structure of the fetus than that performed 2 weeks earlier [3].
Since the 10 th -12 th week of gestation di erent sonographic techniques i.e. transvaginal and transabdominal examination of the fetus along with maternal blood tests may provide information about the pregnancy (meaning the fetus's) development. e woman's health during pregnancy is under separate -di erent control. e prevalence of congenital malformation is around 1-3%. Most of the screening results of the pregnant women performed in the 1st trimester are negative and then the evaluation of the fetus is repeated at the 18 th -20 th week of pregnancy.
An exception is a pregnancy of "high risk" (for instance, the presence of cardiac malformation in the family). In such cases, fetal cardiac examination should be performed earlier -i.e. in the 13 th -15 th week of pregnancy in a reference center [4]. e so-called "early echocardiography" in the majority of cases con rms normal fetal heart structure and allows the safe continuation of pregnancy, relieving the stress of the pregnant woman. e examination of the fetal heart performed at this stage should be treated as preliminary and it requires further con rmation at later stages.
During the rst half of the pregnancy (since the 12th week of gestation) it is also possible to detect severe fetal heart malformations and in such cases some women may decide not to continue their pregnancies [5].
In the middle of pregnancy, an adequately trained physician armored with an "electronic stethoscope" i.e. the appropriate ultrasonographic probe, is able to judge the size and placement of the fetal heart and also the origin of large vessels. However, the fetal heart exam should be performed a er the evaluation of the fetal head, face, skeletal system, thorax, limbs, abdomen, fetal and placental umbilical cord attachment. An important step is the evaluation of the fetal heart position (levocardia?, dextrocardia?, mesocardia?, ectopia ?) , its size, axis, 4-chamber view, mediastinum, big vessel relations [6]. Examples of ultrasound exams are presented in some photographs ( Figure 2, 3,4,5). e majority of congenital heart malformations may not only be detected at this stage of pregnancy but also precisely diagnosed. In the past, only cardiac pathologists were able to do the latter [7]. is was in the era of the medicine of our "fathers and grandfathers".
Taking into consideration that the majority of obstetricians do not get a pediatric or cardiac background during their medical training, such detailed cardiac diagnoses should not be expected from their examinations   geneticists work. Such a team should be prepared to perform diagnostic examinations and therapeutic procedures, both in common, as well as in complex and rare syndromes. e elements of echocardiographic examination in a referral center (including the fetal heart) are shown in Table I. e prevalence of fetal cardiac malformations varies; according to Norwegian data it is 30/10 000 pregnancies [8] while the Chinese reported prevalence from 19/1000 [9] to 27/1000 [10]. ose di erences may re ect the di erences in the methodologies used, including whether ultrasound was used by sonographers (in Europe) or it was fetal echocardiographic examination performed by  a special team (in China). All the authors agreed, however, that the frequency of fetal cardiac malformations is higher than in newborns.
is is also true in Poland. According to the current Polish law, in cases of severe fetal malformation detected and diagnosed in the rst half of pregnancy, or rather until the fetus is able to survive outside the womb, it is the future mother who is in a position to make the decision whether to stop or continue the pregnancy. Terminating the pregnancy means provoking early delivery using prostaglandins on the hospital premises and giving the woman the best chance for the next pregnancy later on.
According to the Polish National Registry of Fetal Cardiac Defects, the majority of pregnant women (over 85%), would like to continue their pregnancies, despite the prenatal diagnosis of heart defect and give the chance of early treatment to the newborn [11].
In the second half of pregnancy, the fetus with a malformation may be monitored using ultrasound during the next few weeks of pregnancy ( Figure 6, 7). e role of perinatal cardiology in saving the life and its quality of fetuses, newborns and children Consultations with pregnant women on the mode of delivery and proceedings with the newborn in the middle of gestation is slowly being given up, as in the majority of cases such questions may be answered by the analysis of fetal development only in the second half of pregnancy and more precisely within weeks or even days predating delivery.
Monitoring of a fetus with a cardiac malformation detected optimally in the middle of the pregnancy consists of serial echocardiographic examinations, including several measurable parameters, and of qualitative assessment. e aim of this procedure is to assess the e ciency of fetal circulation, for instance by using the Cardiovascular Pro le Score (CVPS) (Table II) [12]. Obtaining 10 points on the CVPS means the absence of any haemodynamic alteration either in the fetus with a normal heart or in the fetus with hypoplastic le heart syndrome. It should be remembered, however, that a fetus who obtained 10 points on the CVPS scale, and in whom disturbances in haemodynamics were observed in the next few weeks, may demonstrate a decrease on the CVPS scale to the level of 6-8 points. In cases with 5 < points on the CVPS, the demise of the fetus or newborn should be expected.
In some cases of a threat to the life of the fetus, fetal therapy should be considered -either "through the placenta", where therapeutics is delivered to the pregnant woman either per os or intravenously, or through the umbilical cord, where therapeutics is delivered by cordocentesis. It is also feasible to deliver therapeutics directly to the fetal buttock. Digoxin is the most frequently used therapeutic drug [13]. Before the decision to deliver a drug to a pregnant woman, her cardiological status should be checked and the rule "primum non nocere" is recommended.
In some cases of cardiac malformations, when the haemodynamic state of the fetus is exacerbated and polyhydramnios is observed, several procedures should be considered -i.e. the removal of excess amniotic uid or the delivery of albumins directly to the fetus, percutaneous balloon valvuloplasty (aortic or pulmonary) or dilatation of foramen ovale. All those procedures are plagued by an increased uterine contractility a er the 28th week. Technically, the procedure may be successfully performed but if premature delivery occurs 10-14 days a erwards, it is treated as a complication of intrauterine intervention. Premature delivery in a newborn with a Maria Respondek-Liberska cardiac malformation deprives him or her of the chance to leave the hospital early in up to 60% cases, according to our data from 2017 [14]. e goal is that a pregnancy encumbered with fetal heart malformation should optimally continue to natural delivery at term, with a birth weight >3000 g and a good Apgar score, in a prenatal cardiology center, which collaborates with obstetrical, neonatology, pediatric cardiology and cardiac surgery units. Whether delivery should be vaginal or by Cesarean section is dependent on the status of the pregnant woman and fetus. Echocardiographic monitoring in the second trimester of pregnancy should be performed between the 20th and the 32nd week every 4 th week, then every three weeks (between the 32th and the 35 th week), every second week (between 36 th and the 38 th week) and nally, every week, or even more frequently depending on the cardiac pathology detected. It is most important to observe the status of foramen ovale, the development of pulmonary vessels and ow through the ductus arteriosus.
Independently of echocardiographic monitoring of the fetal heart, the pregnant woman remains under the care of an obstetrician, while a perinatal cardiologist serves as a consultant. For instance, if we deal with fetal cardiac malformation in the form of the common atrio-ventricular canal or double outlet right ventricle, with normal fetal biometry and CVPS 10 and a stable status of the fetus between the 20 th and the 36 th week of pregnancy, the number of fetal echocardiographic examinations performed in the second half of pregnancy should amount to 2 or 3. e fetus may be born naturally (provided there are no other obstetrical problems, i.e. placenta praevia) and a neonatologist and obstetrician should be present at the delivery.
If the stenotic aortic valve is present in a fetus, rst with 20 mmHg gradient (at the 24 th week), and 30 mm of Hg gradient (at the 28 th week), and 40 mm of Hg gradient (at the 34 th week), echocardiographic monitoring close to term is necessary, because with a gradient in the range of 60-70 mm of Hg before delivery, the newborn would require balloon valvuloplasty a few hours a er delivery. e earliest procedure at our hospital was performed 2 hours a er delivery. us, in such cases the time of Cesarean section and availability of a room to perform valvuloplasty should be coordinated in advance, before the time of birth.
Several years ago, we suggested a new classi cation of fetal cardiac malformations, useful in prenatal cardiology [15,16]. e old type classi cation is based on the anatomical details of the fetal heart and still is very important. For years the most frequent type of fetal heart defect in Poland has been Hypoplastic Le Heart Syndrome (Table III). However, what is important in fetal heart defects is not only the anatomy but also the fetus' haemodynamic status and prognosis for the newborn, just a er birth. erefore, a new classi cation for the types of fetal heart defects at the end time of gestation is recommended, as well as the composition of the team present during delivery (Table IV). For instance, in case of fetal cardiac malformation in the form of transposition of great arteries with broad foramen ovale and broad patent ductus arteriosus, the newborn may be delivered naturally and he or she would not be in good clinical condition e role of perinatal cardiology in saving the life and its quality of fetuses, newborns and children for several hours a er delivery. In contrast, a fetus with the same malformation with restricted foramen ovale and premature closure of ductus arteriosus should be treated di erently. Such a situation demands a planned Cesarean Section and urgent Rashkind procedure.
In Poland, like in other countries, the most frequent cardiac malformation is le heart hypoplasia [11]. Among the ve most frequent fetal heart malformations in Poland are Fallot syndrome and transposition of the great arteries, while in foreign statistics it is septal defect, including common atrioventricular canal. ose di erences re ect both the high level of obstetric screening and basic fetal examination in Poland, which, in turn, re ects the appropriate competences of the physicians awarded the Certi cate of the FETAL HEART Examination (the list of such certi cates is on www. orpkp.pl).

Maria Respondek-Liberska
In the Lodz center, in addition to the screening of the fetal heart, we launched a new classi cation taking into account prenatal cardiology rules [15], which is similar to the American risk-strati ed care of newborns with congenital heart disease determined by fetal echocardiography but was introduced earlier [16]. is classi cation enables non-specialists (i.e. obstetricians, neonatologists, nurses, midwifes and parents) to prepare for delivery and to follow-up on the newborn in the rst days a erwards (Table IV).
In practice, we also encounter situations where cardiac malformation is diagnosed in the third trimester in a fetus developing normally in the rst and second trimester. In such cases, estimation of the cardiac structure and haemodynamic status is much more di cult than in cases diagnosed and known since the middle of the pregnancy. is is due to the poor penetration of ultrasounds, which makes it di cult to obtain legible pictures. A prenatal cardiologist must obtain appropriate images, interpret them correctly and obtain a clear acoustic signal from di erent points of the fetal heart auscultation. e latter is obstructed by the position of the fetus, calci cation of the fetal bones, good development of fetal lungs, position of the placenta and the pregnant woman's weight over 90 kg. In both cases, appropriate prenatal diagnosis, estimation of the fetus' haemodynamic status, recommendation for delivery and predictions for the newborn are much more di cult and could be less precise.
It could also happen that a newborn is born with cardiac malformation despite several screening ultrasonographic exams, blood tests and biochemical results within normal limits; such a situation is unexpected for both the parents and medical personnel and the diagnosis of cardiac malformation remains in the hands of a neonatologist and paediatric cardiologist. Transportation of a newborn with cardiac malformation not diagnosed prenatally should be regarded as a failure of prenatal medicine. In such cases as common atrio-ventricular canal, delayed diagnosis does not have any consequences for the newborn, apart from stress for the mother and father, but in cases of critical stenosis of the aorta, delivery not taking place in a neonatological-cardiological unit, transportation of the newborn and delayed valvuloplasty may mean a cardiosurgical procedure. It may also result in neurological complications, long lasting rehabilitation, and nally, the newborn's demise.
In the prenatal period, cardiological problems are not merely malformations, or cardiac fetal insu ciency. Fetal arrhythmias may also be present: (extrasystole, tachycardia or atrio-ventricular blocks).
ese are problems typical for multiple fetal pregnancies, i.e. the twin-twin transfusion syndrome, conjoined twins and haemodynamic complications of twin demise in multiple pregnancies [17,18]. e cardiological status is crucial in cases of extracardiac malformation, like duodenal atresia, arthrogryposis or renal malformations. Prognosis in cases of extracardiac malformations o en depends on the cardiac status.
Obstetricians and perinatologists should be aware of possible fetal cardiac problems, particularly in cases of abnormal CTC and atypical images of ows by Doppler in peripheral fetal vessels. Better interpretation and prevention of premature deliveries brings better results; in contrast relying on false results from less precise examinations makes prognosis worse. Investment in prenatal diagnosis and prenatal therapy also has a nancial dimension because better results may be obtained in a shorter time of hospital stay. As we demonstrated for a newborn with critical aortic stenosis diagnosed prenatally, normal delivery at the 39th week of gestation, and balloon valvuloplasty performed on the rst day of life, the newborn was hospitalized at the intensive care unit for 2 days and altogether for 18-20 days in the hospital. In contrast, a newborn with the same type of cardiac malformation but without prenatal diagnosis and premature delivery and unsuccessful balloon valvuloplasty at 8 days, had a cardiosurgical procedure, e role of perinatal cardiology in saving the life and its quality of fetuses, newborns and children  was hospitalized at the intensive care unit and discharged a er 3 months of hospitalization [19].
Taking into account all the above-mentioned problems, state consultants and teams writing board specialization tests should be asked whether there is enough teaching of prenatal cardiology and whether it should perhaps be more broadly covered in the undergraduate teaching of medical students [20].
Institutional bases of prenatal cardiology were created some 15 years ago in Poland within the framework of the Ministry of Health "Cardio-Prenatal" program headed by state consultant Prof. Wanda Kawalec. e Polish Registry of Fetal Cardiological Problems was created (www. Orpkp.pl [21]). Within this Registry, some 7000 records were stored up to 2017 and a group of 70 physicians were awarded certi cates as FETAL HEART Examination specialists. It was also stressed that prenatal cardiology is becoming an independent branch of medicine including elements of obstetrics, neonatology, pediatric cardiology, radiology and genetics.